pet imaging of radiolabeled anti-hiv-1 envelope monoclonal antibody (vrc01)

Conditions: HIV-1-infection

Summary: this is a single center exploratory imaging study involving one intravenous microdose of 89zr-dfo-vrc01 followed by whole-body pet-mr imaging in hiv infected individuals and healthy volunteers. imaging data will be obtained from up to four static pe-mr images in order to determine dosimetry and temporal tissue uptake/tissue distribution of 89zr-dfo-vrc01. this is not a treatment study of the biological activity of 89zr-dfo-vrc01 to impact hiv persistence.

this will be a single-center pilot study to determine dosimetry and tissue uptake/distribution and pharmacokinetics of 89zr-vrc01. up to 18 uninfected and hiv-infected subjects who are either taking or not taking art will receive a small iv dose of 89zr-vrc01. after administration of iv 89zr-vrc01, subjects will undergo up to 4 whole body pet/mr imaging at 2, 6, 24 and 72-120h to determine the pharmacokinetics and radiation dose exposure. the study involves two phases with the second phase only to be performed only if a difference between pet activity in one or more region of interest can be determined between participant groups phase i (hiv infected, viremic participants and healthy volunteers). initially, up to 6 individuals with plasma hiv rna levels \>1,000 copies/ml and up to 6 hiv-uninfected individuals will be administered 89zr radiolabeled vrc01 followed by pet-mr imaging as above (phase 1). if differences in pet activity in one or more imaging region of interest can be identified between infected and uninfected individuals, up to 6 individuals on suppressive art will be administered 89zr radiolabeled vrc01 followed by pet-mri (phase 2). timing of the pet-mr scans will be determined based on the data from phase 1.

Eligibility criteria:
inclusion criteria: study phase 1 1. age ≥18 years, and 2. hiv uninfected, or 3. hiv infection, and 4. has an hiv viral load measurement within 12 months of study entry of \>40 copies/ml, and 5. hiv-1 envelope rna or dna consensus sequence from peripheral blood suggestive of vrc01 binding activity (hiv infected participants only) study phase 2 1. age ≥18 years, and 2. hiv infection, and 3. initiated a combination art regimen and has hiv viral load measurements below the detection limit of a clinically approved pcr-based assay (e.g. \<40 hiv-1 rna copies/ml of blood), or 4. hiv infection, and 5. has an hiv viral load measurement within 12 months of study entry of \>40 copies/ml, and 6. hiv-1 envelope rna or dna consensus sequence from peripheral blood suggestive of vrc01 binding activity, or 7. hiv uninfected exclusion criteria: study phase 1 1. for patients planning to be imaged on pet-mr scanner, exclusion criteria will include any contra-indication to mri, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia 2. any medical condition that would compromise the imaging acquisition, in the opinion of the investigator 3. patients who have had a study involving radiation within six months of enrolling in this study 4. patients who are pregnant (female patients of childbearing age will be tested prior to injection of imaging agent - positive test will exclude from participating in the study) 5. screening absolute neutrophil count \ 100 units/l, alanine aminotransferase \>100 units/l. 6. absolute cd4+ t cell count \<100 cells/μl (hiv infected individuals only) 7. serious illness requiring hospitalization or parental antibiotics within the preceding 3 months. 8. current hiv-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis study phase 2 1. for patients planning to be imaged on pet-mr scanner, exclusion criteria will include any contra-indication to mri, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia 2. any medical condition that would compromise the imaging acquisition, in the opinion of the investigator 3. patients who have had a study involving radiation within 12 months of enrolling in this study 4. patients who are pregnant (female patients of childbearing age will be tested prior to injection of imaging agent - positive test will exclude from participating in the study) 5. screening absolute neutrophil count \ 100 units/l, alanine aminotransferase \>100 units/l. 6. absolute cd4+ t cell count \<100 cells/μl (hiv infected individuals only) 7. serious illness requiring hospitalization or parental antibiotics within the preceding 3 months. 8. current hiv-related opportunistic infection such as pneumocystis pneumonia, disseminated microbacterial infection, invasive cryptococcal disease, candidal esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis

Keywords: hiv-1-infection pet scan mri viremia antiretroviral therapy